Clinical development program initiated to confirm the safety of modified Fluvax® in young children.

The findings of bioCSL’s multi-year investigation into the cause of the unexpected adverse events associated with its Fluvax® influenza vaccine in 2010 were today published in two separate papers in the peer-reviewed journal Vaccine.

The publications describe an extensive and highly complex investigation that involved international collaborators and was closely monitored by the TGA and the FDA. The findings have led bioCSL to modify its manufacturing process for Fluvax® and to initiate a clinical development program to confirm the safety of the modified vaccine in young children.

During the influenza season of 2010, Fluvax® was associated with a significant increase in reports of fever-related (febrile) convulsions in young children compared to previous seasons. Fluvax® has not been licensed for use in children under 5 years of age since these events. In response, bioCSL undertook a comprehensive, multifaceted investigation comprising clinical data analyses, manufacturing reviews and scientific studies involving over 200 separate laboratory experiments.

The investigation found that as a result of bioCSL’s standard method of manufacture, virus components contained in the 2010 formulation of Fluvax® combined to overstimulate the immune system of some young children, triggering increased fever and fever-related convulsions. Further, these laboratory studies showed that increasing the levels of virus splitting agent used in the bioCSL manufacturing process addresses the potential for Fluvax® to generate excessive febrile reactions.

After successfully manufacturing Fluvax® using increased levels of virus splitting agent, bioCSL conducted a clinical study in adults which confirmed this modification had no negative impact on the immunogenicity of the vaccine. Following consultation with regulators, bioCSL has now implemented increased levels of virus splitting agent into its standard method of manufacturing for Fluvax®.

“As Australia’s only onshore manufacturer of influenza vaccine, we know how important it is for us to be able to produce a seasonal flu vaccine that can be safely used in all age groups,” said Dr John Anderson, General Manager of bioCSL.

“This is why we have continued to work to solve the problem and have now implemented the manufacturing changes we believe will ultimately address the safety concerns associated with the use of bioCSL’s Fluvax® in children.”

“The next step is proving our scientific findings through clinical studies, and until that happens, I want to stress that bioCSL’s Fluvax® must not be used in children under 5 years of age and that restrictions also remain in place ufor the use of Fluvax® in those aged 5 to 9 years.”

“We recognise that the events that took place in 2010 and the ongoing uncertainty about the cause have been very concerning to the public. The investigations have been extremely complex and it is of some relief to have reached this point. Our conclusions now give us a clear path forward which we intend to pursue to the fullest,“ Dr Anderson said.

Current age restrictions for Fluvax1 Fluvax® must not be used in children under 5 years of age. Fluvax® should only be used in children aged 5 to under 9 years based on careful consideration of potential benefits and risks to the individual and if no alternative is available. Fluvax® continues to have an acceptable safety profile in people aged 10 years and over.